Stability of non-canonical nucleic acid structure as a potential modulator of cell fate

Cellular morphological changes occur during cell life and diseases, such as senescence and cancer. Although the cellular conditions should be varied with the morphology changes, there have been no attempts to understand the cellular morphological changes by focusing on the intracellular molecular environment and elucidating the behaviour of nucleic acids. Nucleic acids can form hierarchical secondary and higher-order structures due to intermolecular interactions and other factors. Additionally, a number of important discoveries indicate a link between the effects of intracellular cations, hydration, and metabolic products on the stability of nucleic acid structures and diseases, such as cancer. Thus, changes in gene expression by environments can trigger morphological changes in cells. To elucidate the mechanisms of intracellular gene expression governed by nucleic acid behaviour, it is extremely important to analyse the stability of nucleic acid structures in the whole cell or local cellular spaces by manipulating the actions of small molecules, such as cations, water, and metabolic products. This review article describes the research background and latest progress in controlling senescence and cancer by modulating gene expression based on the prediction of intracellular nucleic acid behaviour, with a focus on the effects of cations, hydration, and metabolites on intracellular nucleic acid structures and their stability.